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Isovaleryl‐CoA Dehydrogenase: Dehydrogenate This!
Author(s) -
Grabon Nick,
Bougie Beth,
Cira Matt,
Erovick Colin,
Fahey Anne,
Jeletz Kelsey,
Kukla Eleanore,
Murphy Matt,
Rohman Tim,
Sass Alyssa,
Tiffany Laura,
Wolff Sam,
Tiffany Karen,
Kim JungJa
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.lb117
Subject(s) - substrate (aquarium) , leucine , acyl coa dehydrogenase , enzyme , biochemistry , cofactor , flavoprotein , chemistry , dehydrogenase , biology , amino acid , ecology
Although rare, isovaleric acidemia (IVA) is a potentially fatal metabolic disorder that affects one in every 250,000 people in the US. IVA results from lack of an enzyme, isovaleryl‐CoA dehydrogenase (IVD), involved in the breakdown of leucine. Without this enzyme, leucine catabolism stops and organic acids accumulate within the body, causing symptoms of IVA, including vomiting, diarrhea, and fatigue. IVD belongs to a family of related enzymes called acyl‐CoA dehydrogenases. IVD catalyzes the dehydrogenation, or removal of a pair of hydrogen atoms, of a small, branched‐chain substrate, isovaleryl‐CoA, during the third step of leucine catabolism. Glutamate 254 of IVD removes one hydrogen as a proton from the substrate, and flavin adenine dinucleotide, FAD, a cofactor of the enzyme, takes away the other hydrogen from the substrate. The three‐dimensional structure of IVD, as determined through X‐ray diffraction, illustrates how a small‐branched chain substrate is able to fit into the active site of this enzyme and enables further investigation of how mutation of the IVD gene could affect IVD function, thus resulting in IVA. To further understand the structural impact on substrate specificity, a physical model of IVD has been designed and built by the Cedarburg High School SMART (Students Modeling a Research Topic) Team using 3D printing technology. Supported by a grant from NIH‐NCRR‐SEPA.